OBJECTIVE: (i) To examine the triglyceride glucose (TyG) index (Ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) and its relationship to in vivo insulin sensitivity in obese adolescents (OB) along the spectrum of glucose tolerance and (ii) to compare TyG index with triglyceride/high-density lipoprotein TG/HDL and 1/fasting insulin (1/IF ), other surrogates of insulin sensitivity.
PATIENTS AND DESIGN: Cross-sectional data in 225 OB with normal glucose tolerance (NGT), prediabetes (preDM), and type 2 diabetes (T2DM) who had a 3-h hyperinsulinemic-euglycemic clamp and fasting lipid measurement.
RESULTS: Insulin-stimulated glucose disposal (Rd) declined significantly across the glycemic groups from OB-NGT to OB-preDM to OB-T2DM with a corresponding increase in TyG index (8.3 ± 0.5, 8.6 ± 0.5, 8.9 ± 0.6, p
METHODOLOGY: The patients were 487 non-diabetic Malay women who had an uncomplicated antenatal course and delivered healthy singleton babies at term. Cord blood and maternal post-partum venous blood samples were taken for assay of serum cholesterol and triglyceride concentrations using standard enzymatic methods.
RESULTS: Maternal total serum cholesterol concentrations (mean +/- SD; 7.5 +/- 2.5 mmol/L) were higher than in other reported series (range of published means 5.2-6.5 mmol/L) with a correspondingly low high-density lipoprotein (HDL): total cholesterol ratio. The mean cord blood total serum cholesterol (1.7 +/- 1.0 mmol/L) was consistent with previously reported population means (1.5-1.9 mmol/L) but there was a relatively high low-density lipoprotein (LDL)-cholesterol and depressed HDL: cholesterol ratio. Significant correlations between maternal and neonatal serum total (P = 0.038) and especially HDL-cholesterol (P < 0.001) were observed. Maternal and cord blood serum triglyceride levels were comparable to those in other series.
CONCLUSIONS: These cross-sectional data provide evidence that abnormal serum cholesterol profiles are found in pregnant Malay women and their neonates which may have implications for the prevalence of macrovascular disease in the Malay population.
OBJECTIVE: The primary study objective was to evaluate the postprandial fate of tocotrienols and alpha-tocopherol in human plasma and lipoproteins.
DESIGN: Seven healthy volunteers (4 males, 3 females) were administered a single dose of vitamin E [1011 mg palm tocotrienol-rich fraction (TRF) or 1074 mg alpha-tocopherol] after a 7-d conditioning period with a tocotrienol-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8, and 24 h after supplementation. Concentrations of tocopherol and tocotrienol isomers in plasma, triacylglycerol-rich particles (TRPs), LDLs, and HDLs were measured at each interval.
RESULTS: After intervention with TRF, plasma tocotrienols peaked at 4 h (4.79 +/- 1.2 microg/mL), whereas alpha-tocopherol peaked at 6 h (13.46 +/- 1.68 microg/mL). Although tocotrienols were similarly detected in TRPs, LDLs, and HDLs, tocotrienol concentrations were significantly lower than alpha-tocopherol concentrations. In comparison, plasma alpha-tocopherol peaked at 8 h (24.3 +/- 5.22 microg/mL) during the alpha-tocopherol treatment and emerged as the major vitamin E isomer detected in plasma and lipoproteins during both the TRF and the alpha-tocopherol treatments.
CONCLUSIONS: Tocotrienols are detected in postprandial plasma, albeit in significantly lower concentrations than is alpha-tocopherol. This finding confirms previous observations that, in the fasted state, tocotrienols are not detected in plasma. Tocotrienol transport in lipoproteins appears to follow complex biochemically mediated pathways within the lipoprotein cascade.
OBJECTIVE: To analyze trends in levels of lipids and apolipoprotein B in US youths during 18 years from 1999 through 2016.
DESIGN, SETTING, AND PARTICIPANTS: Serial cross-sectional analysis of US population-weighted data for youths aged 6 to 19 years from the National Health and Nutrition Examination Surveys for 1999 through 2016. Linear temporal trends were analyzed using multivariable regression models with regression coefficients (β) reported as change per 1 year.
EXPOSURES: Survey year; examined periods spanned 10 to 18 years based on data availability.
MAIN OUTCOMES AND MEASURES: Age- and race/ethnicity-adjusted mean levels of high-density lipoprotein (HDL), non-HDL, and total cholesterol. Among fasting adolescents (aged 12-19 years), mean levels of low-density lipoprotein cholesterol, geometric mean levels of triglycerides, and mean levels of apolipoprotein B. Prevalence of ideal and adverse (vs borderline) levels of lipids and apolipoprotein B per pediatric lipid guidelines.
RESULTS: In total, 26 047 youths were included (weighted mean age, 12.4 years; female, 51%). Among all youths, the adjusted mean total cholesterol level declined from 164 mg/dL (95% CI, 161 to 167 mg/dL) in 1999-2000 to 155 mg/dL (95% CI, 154 to 157 mg/dL) in 2015-2016 (β for linear trend, -0.6 mg/dL [95% CI, -0.7 to -0.4 mg/dL] per year). Adjusted mean HDL cholesterol level increased from 52.5 mg/dL (95% CI, 51.7 to 53.3 mg/dL) in 2007-2008 to 55.0 mg/dL (95% CI, 53.8 to 56.3 mg/dL) in 2015-2016 (β, 0.2 mg/dL [95% CI, 0.1 to 0.4 mg/dL] per year) and non-HDL cholesterol decreased from 108 mg/dL (95% CI, 106 to 110 mg/dL) to 100 mg/dL (95% CI, 99 to 102 mg/dL) during the same years (β, -0.9 mg/dL [95% CI, -1.2 to -0.6 mg/dL] per year). Among fasting adolescents, geometric mean levels of triglycerides declined from 78 mg/dL (95% CI, 74 to 82 mg/dL) in 1999-2000 to 63 mg/dL (95% CI, 58 to 68 mg/dL) in 2013-2014 (log-transformed β, -0.015 [95% CI, -0.020 to -0.010] per year), mean levels of low-density lipoprotein cholesterol declined from 92 mg/dL (95% CI, 89 to 95 mg/dL) to 86 mg/dL (95% CI, 83 to 90 mg/dL) during the same years (β, -0.4 mg/dL [95% CI, -0.7 to -0.2 mg/dL] per year), and mean levels of apolipoprotein B declined from 70 mg/dL (95% CI, 68 to 72 mg/dL) in 2005-2006 to 67 mg/dL (95% CI, 65 to 70 mg/dL) in 2013-2014 (β, -0.4 mg/dL [95% CI, -0.7 to -0.04 mg/dL] per year). Favorable trends were generally also observed in the prevalence of ideal and adverse levels. By the end of the study period, 51.4% (95% CI, 48.5% to 54.2%) of all youths had ideal levels for HDL, non-HDL, and total cholesterol; among adolescents, 46.8% (95% CI, 40.9% to 52.6%) had ideal levels for all lipids and apolipoprotein B, whereas 15.2% (95% CI, 13.1% to 17.3%) of children aged 6 to 11 years and 25.2% (95% CI, 22.2% to 28.2%) of adolescents aged 12 to 19 years had at least 1 adverse level.
CONCLUSIONS AND RELEVANCE: Between 1999 and 2016, favorable trends were observed in levels of lipids and apolipoprotein B in US youths aged 6 to 19 years.
METHODS: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.
RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.
CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.
IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.